TGF-β Signaling as a Pathological Continuum Linking Idiopathic Pulmonary Fibrosis and Lung Cancer

Area of Science:

• Pulmonary Medicine
• Cellular Biology
• Pathophysiology

Background:

• Transforming growth factor-β (TGF-β) signaling is crucial for lung homeostasis, including repair and remodeling.
• Persistent or dysregulated TGF-β activation is implicated in idiopathic pulmonary fibrosis (IPF) and lung cancer.
• These diseases are often studied separately, potentially obscuring shared TGF-β-driven mechanisms.

Purpose of the Study:

• To propose a unifying framework for IPF and lung cancer as endpoints of a shared TGF-β-driven pathological continuum.
• To highlight how TGF-β signaling duration and intensity dictate cellular outcomes.
• To reframe TGF-β signaling as a time-dependent disease modifier.

Main Methods:

• Synthesis of experimental, translational, and clinical findings.
• Review of literature on TGF-β signaling in lung injury, fibrosis, and cancer.
• Integration of data to establish a pathophysiological continuum.

Main Results:

• TGF-β signaling dynamics determine outcomes ranging from repair to fibrosis and tumorigenesis.
• Chronic TGF-β signaling promotes epithelial plasticity, fibroblast fixation, immune suppression, and genomic instability.
• IPF and lung cancer can be viewed as divergent endpoints of a shared TGF-β-mediated process.

Conclusions:

• A unified pathophysiological model integrating fibrosis and tumorigenesis is proposed.
• TGF-β signaling acts as a time-dependent modifier, not a disease-specific factor.
• Targeting specific TGF-β signaling windows may offer therapeutic strategies to intercept disease progression.